Δ9-Tetrahydrocannabinol (THC) is naturally found in cannabis. THC has been reported to have use as an analgesic, for instance for patients suffering from rheumatoid arthritis. A side effect of THC is its psychoactive activity. Further, conventionally THC is administered by smoking, which may be detrimental to general health, in particular to the lungs and the coronary system.
WO 89/01332 describes an acidic metabolite of THC, wherein the methyl group at the 9-position, a major metabolite formed in humans and other mammals, is substituted by a carboxyl group. This metabolite is reported to be non-psychoactive. Its use as a therapeutic agent for such purposes as the treatment of chronic pain and tissue inflammation often associated with illnesses such as rheumatoid arthritis is suggested. The Examples show a mouse hot plate test for analgesia, which indicates that, in mice, the metabolite shows about the same analgesic activity as THC and a somewhat lower activity than Naproxen. The Examples further indicate that the metabolite does not induce the formation of gastric lesions in an animal test under conditions wherein aspirin does.
In a review by Bhargava (Gen. Pharmac. (1978) 9(4):195-213), potential uses of cannabinoids are mentioned in rather general terms. Bhargava mentions that several cannabinoids have been pharmacologically tested, without disclosing in any detail, a specific medical activity for carboxylated THCs (THC acids), such as Δ9-tetrahydrocannabinolic acid or the like. In addition, reference is made to the analgesic activity of THC and several other cannabinoids compared to morphine. THC is reported to perform equi-analgesic with morphine, but other tested cannabinoids are reported to be much less potent or even inactive.
Williamson and Evans (Drugs 2000, December 60(6):1303-1314 discuss in general terms a potential clinical use of cannabis. The specific use of THC acids, such as Δ9-tetrahydrocannabinolic acid or the like, as the active pharmaceutical ingredient, is not disclosed.
GB-A 2 384 707 relates to the use of a cannabinoid acid, in particular cannabidiol (CBD) and cannabidiol acid (CBDA) for use as an active pharmaceutical substance in the treatment of nausea, vomiting, emisis and motion sickness. The compounds may be obtained by extraction from cannabis. As a result of the extraction, relatively small amounts of THC-acids may be present in the extract, but the use of a THC-acid as an active pharmaceutical substance is not mentioned.